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Biomedical subjects

G Brook

Publications and source records attributed to G Brook.

At least 37 records · Page 2Linked to original sources

Efficacy and safety of pravastatin once daily in primary moderate hypercholesterolemia: the Israeli experience.

Seventy-seven hypercholesterolemic patients participated in a 26-week, multicenter, randomized, double-blind, placebo-controlled study that investigated the efficacy and safety of pravastatin therapy. All patients had primary moderate hypercholesterolemia (total cholesterol 200-300 mg/dl, at the end of a 6-week dietary run-in period) and two additional coronary risk factors. Pravastatin, 20-40 mg/day given at bedtime, reduced total cholesterol by 19-22%, LDL-cholesterol by 24-30%, triglycerides by 10-30% and increased HDL-cholesterol by 9-13%. The drug caused mild elevation in alanine aminotransferase and aspartate aminotransferase. Almost all these elevations were within normal limits and no patient was clinically symptomatic. No other significant differences were observed between the pravastatin and the placebo-treated groups with regard to other adverse effects and to patient compliance and withdrawal. It is concluded that pravastatin has a beneficial effect on the lipid profile and that the drug is safe and well tolerated.

Adult↗

Treatment of hepatitis B virus infection with interferon. Factors predicting response to interferon.

Several randomised controlled trials have been undertaken to evaluate the efficacy of alpha-interferon in the therapy of chronic hepatitis B. In patients with HBe antigen-positive disease acquired in adult life the response rates vary from 25-50%. In those infected at birth, response rates are lower. Twenty-one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given alpha-interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks, a negative anti-human immunodeficiency virus antibody status (p less than 0.001), chronic active hepatitis on liver biopsy (p less than 0.005), high AST level (p less than 0.001), low hepatitis B virus DNA level (p less than 0.001) and a history of acute hepatitis (p less than 0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p less than 0.05). The most reliable combination of predictive factors was a negative anti-human immunodeficiency virus antibody status, with either a positive history of acute icteric hepatitis and AST greater than 45 IU per liter or no history of acute icteric hepatitis and AST greater than 85 IU per liter, which predicted response in 77% with a specificity of 79% (p less than 0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of less than 2 years duration (p less than 0.001).

Adult↗

Incidence, mortality, and case-fatality rate of stroke in northern Israel.

We studied the incidence and mortality of stroke in northern Israel to determine possible reasons for the differences previously found in mortality from this condition between the sex and ethnic groups in Israel as a whole. We identified 1,149 cases of stroke during 1984. While the age-standardized incidence was higher in men, the case-fatality rate was twice as high in women. After controlling for ethnic origin, we found that incidence was higher only in men of Western origin, while the female rates were higher in women of Asian and North African extraction. The case-fatality rate was substantially higher in women in all ethnic groups. These differences, especially in relation to the case-fatality rate, have important implications for health services in relation to both possible preventive action and to management of the acute disease phase.

Age Factors↗

Platelet-modified low density lipoprotein induces macrophage cholesterol accumulation and platelet activation.

Low density lipoprotein (LDL), modified by chemical or biological means, was shown to induce macrophage cholesterol accumulation. The cholesterol and protein contents of LDL were decreased (by 10 and 15%, respectively) by incubation of the LDL for 2 h at 37 degrees C with normal washed platelet suspension or with platelet-conditioned medium; these decreases were not affected by platelet activation. The platelet-modified LDL caused a greater increase (by up to 15%) in collagen-induced, in vitro platelet aggregation than control LDL. Incubation of mouse peritoneal macrophages with platelet-modified LDL for 18 h at 37 degrees C resulted in an elevation of the macrophage cholesterol ester content (by 35-50%) as well as an increase in the cholesterol esterification rate (by 40-70%), compared with the effect of control LDL. Macrophage cholesterol synthesis, however, was significantly decreased (by 40-50%), compared with the effect of control LDL. The effect of LDL treated by platelet-conditioned medium was similar to that of platelet-modified LDL. The effect of platelet-modified LDL on macrophage cholesterol esterification was maximal within 24 h of incubation, and it was not significantly affected by inhibition of cholesterol synthesis. The platelet-modified LDL was taken up by the macrophages in a saturable fashion and its uptake was competitively inhibited by LDL, but not by acetylated LDL. We conclude that platelet-modified LDL interacts with the LDL receptor and induces macrophage cholesterol accumulation. Since the modified lipoprotein induces in vitro foam cell formation and platelet activation, platelet-modified LDL could be considered to be pro-atherogenic.

Animals↗

Major adverse reactions to a short course of daily rifampicin.

Hypersensitivity, dyspnoea and shock reactions to rifampicin in a 24-year-old man are described after a short course of daily treatment for tuberculous lymphadenitis. These combined reactions have not previously been reported after such a short course of therapy. Treatment with fluids, steroids, and antihistamines for the dyspnoea and shock reaction, and withdrawal of rifampicin led to complete recovery. The increased use of rifampicin in short courses may lead to more such reactions being observed.

Adult↗

Effects of Phoneutria nigriventer spider venom on mouse peripheral nerve.

A physiological and morphological study has been made of the effects of the venom of the spider Phoneutria nigriventer on peripheral nerve and skeletal muscle of the mouse. Venom was injected either into the sciatic nerve, via a glass micropipette, or into the calf muscles. Repetitive firing of nerve fibres commenced within seconds of injection and caused fasciculation of muscles and irregular trains of end-plate potentials. These physiological disturbances were associated with swelling of the nodal and paranodal axoplasm and the development of vacuoles in the periaxonal space. The segments of internode between the vacuoles became attenuated, with an increase in the density of axoplasmic organelles and a reduction in axonal calibre. The repetitive firing ceased after 1-3 h with development of conduction block. Both the physiological and the morphological abnormalities gradually resolved and by 24 h nerve conduction and morphology had largely returned to normal. It seems likely that these short-lived abnormalities are a consequence of the influx of sodium ions at the nodes of Ranvier, caused by the action of the venom on sodium channels.

Animals↗

Platelet function and lipoprotein levels after plasma-exchange in patients with familial hypercholesterolaemia.

1. Repeated plasma exchange was carried out on three young patients with severe familial hypercholesterolaemia. There was a 3 week interval between each exchange. After a single exchange, plasma cholesterol, apolipoprotein B and low density lipoprotein-cholesterol levels decreased markedly, but pre-exchange levels were not achieved within 2 weeks. High density lipoprotein-cholesterol and apolipoprotein A-I levels also fell but returned to the original concentration after only 5 days. 2. Platelet aggregation and [14C]serotonin release were increased in all three patients and dropped by 20% and 13% respectively after a single plasma exchange. Platelet function in vitro returned to pre-exchange levels with similar kinetics to that observed with the low density lipoprotein concentration. On removal of 100 g of plasma cholesterol, after repeated exchanges, low density lipoprotein concentration and platelet function were significantly decreased in comparison with values before initiation of plasma exchange. In addition there was a marked regression of xanthoma in all three patients. 3. Since this procedure is instrumental in achieving a negative cholesterol balance as well as inhibiting hypersensitive platelets, it may well result in a downgrading of the atherosclerotic risk.

Adolescent↗

Pericardial rub in pericardial effusion: lack of correlation with amount of fluid.

The relation between the amount of pericardial fluid and the presence of a pericardial rub was examined in 76 patients with echocardiographic evidence of pericardial effusion. A pericardial rub was noted in 4 of 13 patients with small pericardial effusion (less than 100 ml), in 23 of 40 patients with moderate effusion (100 to 500 ml), and in ten of 23 patients with a large effusion. No difference in the amount of fluid was demonstrated in the group of patients with a rub when compared to the group without one. There was a statistically significant relation between the presence of a rub and the cause of the effusion. No inference as to the amount of pericardial fluid should be drawn from the presence or absence of a pericardial rub.

Child↗

Improved glucose tolerance and insulin response in obese and diabetic patients on a fiber-enriched diet.

Twenty-two subjects, six of them obese, five latent diabetics, six overt diabetics, and five control subjects, were given a daily dietary supplement of 16 g guar gum and 10 g pectin for three successive days. Postprandial blood glucose and insulin responses to an initial standard meal and to a fiber-enriched meal given 72 h later were compared. A significant decrease of blood glucose levels was found in all subjects, with maximal response in the obese group. We conclude that supplementing the diet with certain fibers can be regarded as an important therapeutic measure in the treatment of diabetic and obese patients.

Adolescent↗